leukotriene-b4 and Barrett-Esophagus

Epidemiologic studies suggest a reduced risk of esophageal adenocarcinoma in populations with a high consumption of fish, and n-3 fatty acids inhibit experimental carcinogenesis. One possible explanation is the suppression of eicosanoid production through inhibition of cyclooxygenase 2 (COX-2).. The objective was to determine the effects of dietary supplementation with the n-3 fatty acid eicosapentaenoic acid (EPA) on a number of biological endpoints in Barrett's esophagus.. Fifty-two participants with known Barrett's esophagus underwent endoscopy. Biopsy samples were obtained from a recorded level within the area of Barrett's esophagus, and then 27 patients were randomly assigned to consume EPA capsules (1.5 g/d) for 6 mo or no supplement (controls). At the end of this period, patients again underwent endoscopy, and biopsy samples were collected at the same level. Tissue samples were analyzed for mucosal lipid, prostaglandin E2, leukotriene B4, COX-2 protein, and RNA concentrations. Cellular proliferation was also measured, by Ki-67 immunohistochemistry.. The EPA content of esophageal mucosa increased over the study period in the n-3-supplemented subjects and was significantly different from the content in the controls (P < 0.01). There was also a significant decline in COX-2 protein concentrations (measured by immunoblotting) in the n-3 group, and the difference was significant from that in the controls (P < 0.05); no difference in COX-2 RNA concentrations was observed between groups. This change in COX-2 protein was inversely related to the change in EPA content (P < 0.05). There was no significant difference in the change in prostaglandin E2, leukotriene B4, or cellular proliferation between the 2 groups.. Supplementation with EPA significantly changed n-3 fatty acid concentrations and reduced COX-2 concentrations in Barrett's tissue.

Topics: Aged; Barrett Esophagus; Cell Division; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dietary Supplements; Dinoprostone; Eicosanoids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Leukotriene B4; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA

Eicosanoids (prostaglandins and leukotrienes) may contribute to the clinical manifestations of gastroesophageal reflux disease (GERD). In this cross-sectional study, our purpose was to assess the role of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) in the clinical, endoscopic, and histological manifestations of GERD.. Using RIA, we measured ex vivo LTB4 and PGE2 content in esophageal mucosal biopsies from 141 patients with or without gastroesophageal reflux disease who underwent upper endoscopy. Patients were classified as normal symptomatic controls(n = 70), esophagitis stages 1-4 (n = 60), and Barrett's esophagus (n = 11), using clinical, endoscopic, histological, manometric, and esophageal 24-h ambulatory pH criteria.. Mean LTB4 levels were significantly higher in both endoscopically and histologically identified erosive esophagitis and Barrett's esophagus patients, compared with normal controls. In contrast, PGE2 levels did not differ significantly among endoscopic or histological groups. When eicosanoid levels and composite symptom score (frequency score x severity score summed over five symptoms) were analyzed, no significant associations were found between LTB4 or PGE2 levels and the composite symptom score. There was no correlation between tissue eicosanoid levels and either the degree of esophageal acid exposure by ambulatory pH monitoring or the lower esophageal sphincter resting pressure as assessed by esophageal motility. Treatment with omeprazole 20 mg by mouth daily for 6 wk significantly reduced both LTB4 and PGE2 levels (p < 0.05) and was associated with significant improvement of symptoms and the endoscopic and histological appearance of the esophagus in 25 patients.. These results suggest that LTB4, a prominent product of arachidonic acid metabolism in neutrophils, mediates the inflammatory phenomena of reflux esophagitis. The role of LTB4 and PGE2 in the induction of symptoms in patients with GERD and Barrett's esophagus remains unclear.

Topics: Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biopsy; Dinoprostone; Esophagoscopy; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Leukotriene B4; Male; Middle Aged; Monitoring, Ambulatory; Mucous Membrane; Peristalsis; Time Factors